title: Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation.
abstract: The existence of endogenous neural progenitors in the nigrostriatal system could represent a powerful tool for restorative therapies in Parkinson's disease. Sox-2 is a transcription factor expressed in pluripotent and adult stem cells, including neural progenitors. In the adult brain Sox-2 is expressed in the neurogenic niches. There is also widespread expression of Sox-2 in other brain regions, although the neurogenic potential outside the niches is uncertain. Here, we analyzed the presence of Sox-2(+) cells in the adult primate (Macaca fascicularis) brain in naïve animals (N = 3) and in animals exposed to systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine to render them parkinsonian (N = 8). Animals received bromodeoxyuridine (100 mg/kg once a day during five consecutive days) to label proliferating cells and their progeny. Using confocal and electron microscopy we analyzed the Sox-2(+) cell population in the nigrostriatal system and investigated changes in the number, proliferation and neurogenic potential of Sox-2(+) cells, in control conditions and at two time points after MPTP administration. We found Sox-2(+) cells with self-renewal capacity in both the striatum and the substantia nigra. Importantly, only in the striatum Sox-2(+) was expressed in some calretinin(+) neurons. MPTP administration led to an increase in the proliferation of striatal Sox-2(+) cells and to an acute, concomitant decrease in the percentage of Sox-2(+)/calretinin(+) neurons, which recovered by 18 months. Given their potential capacity to differentiate into neurons and their responsiveness to dopamine neurotoxic insults, striatal Sox-2(+) cells represent good candidates to harness endogenous repair mechanisms for regenerative approaches in Parkinson's disease.
authors.affiliation: Laboratory of Regenerative Therapy, Neuroscience Division, Centro de Investigación Médica Aplicada and Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ordoñez
authors.forename: Paz
authors.initials: P
authors.lastname: Moreno-Murciano
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez
authors.forename: Carla
authors.initials: C
authors.lastname: Di Caudo
authors.forename: Iñaki-Carril
authors.initials: IC
authors.lastname: Mundiñano
authors.forename: Iñaki
authors.initials: I
authors.lastname: Carril-Mundiñano
authors.forename: Nerea
authors.initials: N
authors.lastname: Vazquez
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.forename: Rosario
authors.initials: R
authors.lastname: Sanchez-Pernaute
authors.forename: Maria-Rosario
authors.initials: MR
authors.lastname: Luquin
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008252:Macaca fascicularis; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D055748:SOXB1 Transcription Factors; D004298:Dopamine